W. Donald Shields

Surgery for intractable infantile spasms: neuroimaging perspectives.

Summary: Twenty‐three infants and children underwent cortical resection (n= 15) or hemispherectomy (n =8) for intractable infantile spasms. Infantile spasms were present at the time of surgery in 17 of the 23 patients; in six, spasms had evolved to other seizure types during surgical evaluation. Children with a remote history of infantile spasms were excluded from this study. Focal or hemispheric lesions were identified by magnetic resonance imaging in seven children; an additional two showed focal atrophy without a discrete lesion. Positron emission tomography (PET) showed lateralized or localized abnormalities of cerebral glucose utilization in all patients; in 14, PET was the only neuroimaging modality to identify the epileptogenic cortex. When this occurred, neuropathological examination of resected brain tissue typically showed malformative and dysplastic cortical lesions. Focal interictal and/or ictal electrographic abnormalities were present in all patients, and corresponded well with localization from neuroimaging. None of the patients were subjected to chronic invasive electrographic monitoring with intracranial electrodes. At follow‐up (range 4–67 months; mean 28.3 months), 15 children were seizure‐free, three had 90% seizure control, one had 75% seizure control, and four failed to benefit from surgery with respect to seizure frequency.

Infantile spasms: A U.S. consensus report

The diagnosis, evaluation, and management of infantile spasms (IS) continue to pose significant challenges to the treating physician. Although an evidence‐based practice guideline with full literature review was published in 2004, diversity in IS evaluation and treatment remains and highlights the need for further consensus to optimize outcomes in IS. For this purpose, a working group committed to the diagnosis, treatment, and establishment of a continuum of care for patients with IS and their families—the Infantile Spasms Working Group (ISWG)—was convened. The ISWG participated in a workshop for which the key objectives were to review the state of our understanding of IS, assess the scientific evidence regarding efficacy of currently available therapeutic options, and arrive at a consensus on protocols for diagnostic workup and management of IS that can serve as a guide to help specialists and general pediatricians optimally manage infants with IS. The overall goal of the workshop was to improve IS outcomes by assisting treating physicians with early recognition and diagnosis of IS, initiation of short duration therapy with a first‐line treatment, timely electroencephalography (EEG) evaluation of treatment to evaluate effectiveness, and, if indicated, prompt treatment modification. Differences of opinion among ISWG members occurred in areas where data were lacking; however, this article represents a consensus of the U.S. approach to the diagnostic evaluation and treatment of IS.

Depression and Anxiety Disorders in Pediatric Epilepsy

Summary:  Purpose: This study examined affective disorders, anxiety disorders, and suicidality in children with epilepsy and their association with seizure‐related, cognitive, linguistic, family history, social competence, and demographic variables.

Childhood absence epilepsy: behavioral, cognitive, and linguistic comorbidities.

Purpose:  Evidence for a poor psychiatric, social, and vocational adult outcome in childhood absence epilepsy (CAE) suggests long‐term unmet mental health, social, and vocational needs. This cross‐sectional study examined behavioral/emotional, cognitive, and linguistic comorbidities as well as their correlates in children with CAE.

Behavioral Disorders in pediatric epilepsy: Unmet psychiatric need

Summary:  Purpose: This study examined the relation between psychiatric diagnosis and mental health services in children with epilepsy and the associated demographic, cognitive, linguistic, behavioral, and seizure‐related variables.

Postoperative Seizure Control and Antiepileptic Drug Use in Pediatric Epilepsy Surgery Patients: The UCLA Experience, 1986–1997

Summary: Purpose: Young children with refractory symptomatic epilepsy are at risk for developing neurologic and cognitive disabilities. Stopping the seizures may prevent these disabilities, but it is unclear whether resective surgery is associated with adequate long‐term seizure control.

Hemispherectomy for intractable seizures in children: a report of 58 cases

Fifty-eight children who underwent anatomical, functional, or modified anatomical hemispherectomy for intractable seizures from 1986 to 1995 were evaluated for seizure control, motor function, and complications. Age at surgery ranged from 0.3 to 17.3 years (median 2.8 years). Twenty-seven anatomical, 27 functional, and 4 modified anatomical hemispherectomies were performed. Seizure control and motor function in the 50 patients with more than 1 year follow-up revealed a 90% or better reduction in seizure frequency in 44/50 (88%) overall: 19/22 (86%) anatomical, 23/26 (89%) functional, and 2/2 modified anatomical. Motor function of the preoperatively hemiparetic extremities was improved or unchanged postoperatively in 38/50 (76%) of the patients. Complications included one intraoperative death, one late death from shunt obstruction managed elsewhere, late postoperative seizure breakthrough requiring reoperation and further disconnection in 5/27 functional hemispherectomy patients, mild cerebrospinal fluid infections in 3/27 anatomical hemispherectomy patients, and hydrocephalus requiring shunting in 3/27 functional hemispherectomy patients. A review of the literature and comparison of techniques is presented.

Vigabatrin: 2008 update.

Vigabatrin (VGB) is a structural analogue of γ‐aminobutyric acid (GABA) that irreversibly inhibits GABA‐transaminase (GABA‐T), increasing brain levels of GABA. VGB is under assessment for treatment of infantile spasms (IS) and refractory complex partial seizures (CPS). Response can be rapid with spasm cessation following approximately 2 weeks of therapy. Patients with symptomatic tuberous sclerosis (TS) and other patients have achieved spasm cessation. Comparison with ACTH has been performed. Patients with refractory CPS have responded as well. Adverse effects and structural findings on imaging occur with VGB treatment. T2 hyperintensities within brain have been observed. Psychotic disorders or hallucinations have occurred rarely. A specific adverse effects is associated VGB, with a peripheral visual field defect (VFD) detected in some patients. Prevalence and incidence of the VGB‐induced peripheral VFD varied depending on the age of the patient and the extent of exposure to VGB, with 25% to 50% prevalence in adults; the prevalence in children was 15% and retinal defect in infants ranged from 15% to 31%. A bilateral nasal defect may be the first clinical indication and may progress to a concentric, bilateral field defect observed in many affected patients; central visual acuity is almost always preserved. The earliest finding of the first abnormal field examination in adults was after 9 months of treatment; with a mean duration of VGB exposure of 4.8 years. In children, the earliest onset of a first abnormal field examination was after 11 months, with a mean time to onset of 5.5 years. The earliest sustained onset of the VGB‐induced retinal defect in infants was 3.1 months.

Efficacy and Safety of Levetiracetam in Children with Partial Seizures: An Open-label Trial

Summary:  Purpose: To assess the efficacy and safety of levetiracetam (LEV) as adjunctive therapy in children with treatment‐resistant partial‐onset seizures.

l‐Carnitine Supplementation in Childhood Epilepsy: Current Perspectives

Summary: In November 1996, a panel of pediatric neurologists met to update the consensus statement issued in 1989 by a panel of neurologists and metabolic experts on L‐carnitine supplementation in childhood epilepsy. The panelists agreed that intravenous L‐carnitine supplementation is clearly indicated for valproate (VPA)‐induced hepatotoxicity, overdose, and other acute metabolic crises associated with carnitine deficiency. Oral supplementation is clearly indicated for the primary plasmalemmal carnitine transporter defect. The panelists concurred that oral L‐carnitine supplementation is strongly suggested for the following groups as well: patients with certain secondary carnitine‐deficiency syndromes, symptomatic VPA‐associated hyperammonemia, multiple risk factors for VPA hepatotoxicity, or renal‐associated syndromes; infants and young children taking VPA; patients with epilepsy using the ketogenic diet who have hypocarnitinemia; patients receiving dialysis; and premature infants who are receiving total parenteral nutrition. The panel recommended an oral L‐carnitine dosage of 100 mg/kg/day, up to a maximum of 2 g/day. Intravenous supplementation for medical emergency situations usually exceeds this recommended dosage.